PURPOSE: The purpose of this study is to evaluate the safety and efficacy of orally administered voglibose (AO-128) in patients with type II diabetes mellitus for 52 weeks. Long term safety and tolerability are of primary interest in this study. Safety and tolerability will be evaluated by tabulating adverse experiences (clinical and laboratory data) and reasons for study discontinuation. Of secondary interest, the efficacy of AO-128 will be evaluated using changes in glycosylated hemoglobin (HbA1c). Type II diabetes is characterized by fasting hyperglycemia and glucose intolerance, manifested by a steep increase in post-prandial blood glucose concentration and insulin secretion. The goal in treatment of type II diabetes is to achieve normoglycemia, usually through use of diet and exercise therapy or with oral agents such as sulfonylureas (e.g., glipizide), biguanides (metformin), and, most recently, alpha- glucosidase inhibitors (acarbose). Voglibose, an N-substituted derivative of valiolamine, is an alpha-glucosidase inhibitor. The compounds in this class delay digestion of disaccharides and complex carbohydrates by reversible inhibition of alpha-glucosidases in the brush border of the small intestine. The inhibitory activity of voglibose is about 190-270 times more potent than acarbose, which has already received FDA approval. Because it favors inhibition of maltase and sucrase, voglibose is considered to be a selective disaccharidase inhibitor. METHODS: At our site, the patients who enter this open-label extension will have completed the double- blind portion of the study (D-102) or entered D-103 early due to unsatisfactory therapeutic response following randomization in D-102. During this open-label extension, patients will be treated with voglibose 0.5mg tid up to 5 mg tid, and titration of dosage will be based on HbA1c. The study will involve a 52 week treatment period and a 2 week follow up period. Patients will be started on voglibose 0.5 mg tid for the first two weeks of the study and 1.0 mg tid during weeks 3 and 4. Patients will then receive 2.0 mg tid from week 5 to week 20. After 20 weeks, If HbA1c has decreased by <0.3% compared to the patient's baseline the dose will be titrated up to the next highest dose. Patients will return for 9 outpatient visits at 2-8 week intervals during which blood and urine samples will be collected. In addition, at week 52 (the end of the treatment period), a physical exam, fundus photos, and an EKG will be performed. Approximately 1-2 weeks later, patients will return for a follow up visit. RESULTS AND CONCLUSIONS: The study was completed at our site in February 1998. This was a pharmaceutical-sponsored multicenter study and results have not been provided for us to date. SIGNIFICANCE OF THE STUDY AND FUTURE PLANS: As mentioned previously, animal studies have indicated that the inhibitory activity of voglibose is 190 - 270 times more potent than acarbose (a currently marketed alpha-glucosidase inhibitor). Also, human studies (368 volunteers and 1635 patients treated with voglibose) to date have indicated that voglibose significantly reduces the postprandial peak and area under the curve of blood glucose and insulin in a dose-dependent manner. Interim analysis of a placebo-controlled European study in 259 patients with type II diabetes indicates a dose-dependent decrease in glycated HbA1c. The results of this study and D-102 will provide the basis of future studies.